Systemic Renin-Angiotensin-System

This project presents SimBiology model implementation of the systemic Renin-Angiotensin-System that was first developed by Lo et al. and used to investigate the effects of different RAS-modulating therapies. The RAS pathway is crucial for blood pressure and kidney function control as well as a range of other organism-wide functions. The model describes the enzymatic conversion of the precursor protein Angiotensinogen to Angiotensin I and its downstream products Angiotensin 1-7, Angiotensin II and Angiotensin IV. Key pathway effects are triggered by the association of Angiotensin II with the AT1-Receptor. A positive feedback loop connects the Angiotensin II–AT1-Receptor complex with the Angiotensinogen conversion (not shown in the diagram). Enzymatic reactions are modeled as pseudo-unimolecular using enzymatic activities as reaction rates. Degradation reactions are described using protein half-life times. Drug pharmacodynamics are included in the model using the term (1-DrugEffect), where DrugEffect follows a sigmoidal dependence on the Drug concentration, to modify the target enzyme activity.